Date of Award

1995

Degree Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

Department

Electrical and Computer Engineering

Supervisor

Dr. C. Nahmias

Abstract

The physiology of the muscle of the heart (myocardium) can be studied regionally in the living body using positron tomographic techniques. Compounds are labelled with a positron emitting isotope, administered into the circulation, and their distribution in the body is measured with a positron tomograph. This enables the rates of myocardial blood flow and substrate metabolism to be measured regionally in the myocardium of the left ventricle. The accuracy and precision of these measurements are estimated to range from 2% to 15% in a given individual. Much of this variability is due to normal changes in physiological state, or to measurement noise associated with counting statistics. However, additional variability is associated with manual processing, which typically involves specification of the left ventricular myocardium of interest using an interactive visual display. An automated technique of analysis can remove this source of variance, and enable an unbiased evaluation of changes in response to the treatment of heart disease. Results can then be compared objectively between population samples or in single subjects studied under different treatment conditions. By performing appropriate statistical comparisons, a large volume of data is compressed into a form which can be interpreted in an efficient manner.

An automated analysis technique is developed to remove the variability associated with manual processing. Reduction of the measurement variability increases the statistical power to detect physiological changes in the myocardium in different states of health and disease. The position and angular orientation of the left ventricle is determined directly from the measured dataset, so that the regional measurements can be analysed and presented in a standard format. The time course of radioactivity is determined for several hundred volume elements within the left ventricular myocardium, and for a blood region positioned in the ventricular cavity. Depending on the labelled compound and study protocol, various measures of myocardial physiology are computed from these two basic measurements. A technique is developed to compare treatment changes in physiology between population samples, by segmenting equivalent functional tissue regions from the left ventricular myocardium of the sample subjects. A method is also developed to evaluate the statistical significance of changes in single subjects, which may be useful to determine individual clinical responses to treatments. Comprehensive quality assurance outputs are generated, and are used to verify the analysis of all cardiac studies.

The performance of the method was determined using cardiac phantom and human data. The position and angular orientation of the left ventricle were determined to within 2±2 mm and 3±3 degrees of the true values respectively. The detection of treatment changes in a population sample was demonstrated using measurements of myocardial blood flow with ¹³N-labelled ammonia. An increase in blood flow to diseased (ischemic) myocardium in response to nitroglycerin was demonstrated using a quantitative automated approach: a highly significant (p=0.01) difference of 16 ml/min/dg (20% of normal) was detected in a sample group of 14 subjects. The performance of the single subject analysis was verified by measuring the rate at which significant changes occured by chance, which was equal to the theoretical false positive rate. In an individual from the population sample, a significant increase (p=0.001) in myocardial blood flow of approximately 30% was detected in a region of known ischemia, in response to treatment with nitroglycerin. The statistical tools developed in this work can also be used to determine other sources of measurement variability. Reduction of these effects will increase further the power of positron tomography to evaluate objectively the clinical effects and mechanisms of action of cardiac treatments in health and disease.

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